Globally, dengue infections result in more than 20,000 deaths, nearly 500,000 hospitalized cases and anywhere between 50-100 million human infections annually. (1) Dengue infection is caused by one of four immunologically distinct serotypes of the dengue virus (DENV 1-4). The virus is spread by the urban breeding mosquito Aedes aegypti. Usually, infection with any one of the four DENV serotypes leads to mild, self-limiting dengue fever with lifelong immunity to the specific serotype of infection. Epidemiological evidence also indicates that 90% of the severe and potentially fatal dengue diseases, dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) occur during secondary heterotypic infections where the protective antibody from a prior infection takes on a pathogenic role, so-called Antibody Dependent Enhancement (ADE). (2, 3) The antibody response triggers a systemic inflammatory reaction resulting in vascular leakage.
Currently, there is no approved preventive vaccine or antiviral treatment for dengue disease. The World Health Organization has listed dengue fever as an emerging and uncontrolled disease. (4) Hence, there is an urgent medical need for the development of a potent dengue antiviral that is safe for use in humans.